Peripheral blood cells originate from the hematopoietic stem and progenitor cells (HSPC) residing in the bone marrow. Hematopoietic stem and progenitor cells in the bone marrow repeatedly divide and pass through successive stages of differentiation. Then, the resulting mature and functional cells are released from the bone marrow into the bloodstream.
The process of formation and release of blood cells from the bone marrow into the circulation is strictly regulated by a number of biological factors. It is now known that this process can be regulated pharmacologically—administration of G-CSF (ang. granulocyte colony stimulating factor) results in an enhanced production of granulocyte progenitor cells in the bone marrow and their increased release into the bloodstream. This process is called mobilization and has important clinical implications.
Acute decline in cell numbers in the blood is often observed in patients receiving chemotherapy as anti-tumor therapy. It increases the risk of infections which may have serious consequences and interferes with the anticancer treatment. In this case, administration of G-CSF increases mobilization of cells from bone marrow to the blood and restores the number of white blood cells to normal levels.
Another important use of mobilization by G-CSF is the preparation of a donor during HSPC transplantation. Currently cells isolated from peripheral blood are transplanted for the bone marrow reconstruction. The number of transplanted stem cells is crucial for the success of transplantation. In order to increase the number of stem cells circulating in blood G-CSF is administered to donors prior to the blood collection.
Currently for clinical applications for the mobilization of cells into the bloodstream G-CSF analogs (mainly a drug called filgrastim) are used. These are recombinant proteins produced in E. coli. The production of such proteins is complicated and expensive. In addition, G-CSF analogs prepared by this technique are not glycosylated, as are proteins naturally occurring in humans.
Porphyrins are a group of heterocyclic organic compounds consisting of four pyrrole rings connected by methine bridges. In terms of structure, all compounds of this group are derived from the simplest porphyrin called porphine. Synthetic porphyrins are widely used as ligands in the complex compounds used for catalysis. Currently, related compounds are used in medicine: porphyrins in photodynamic therapy and heme arginate in the treatment of acute hepatic porphyria. In clinical trials, tin protoporphyrin was used in the treatment of neonatal jaundice. Use of a porphyrin in photodynamic therapy is disclosed for example in U.S. Pat. No. 5,776,966 and WO9324127, which describe a method for selectively reducing the level of active leukocytes in blood or bone marrow, by administering a green porphyrin, and then subjecting the blood or bone marrow to radiation absorbed by those porphyrins. This therapy is designed especially for people suffering from autoimmune diseases and patients infected with HIV. Metal protoporphyrins, including cobalt protoporphyrin, are disclosed in patent application US2012/0039987 for the use for anti-inflammatory diseases of the nervous system, atherosclerosis and diabetes. Cobalt porphyrins have been proposed for use in the treatment of obesity (U.S. Pat. No. 5,149,697, U.S. Pat. No. 5,192,757). Porphyrins have not yet been combined with the process of mobilization of cells.